Elsevier

Brain, Behavior, and Immunity

Volume 90, November 2020, Pages 311-318
Brain, Behavior, and Immunity

Interleukin-8 dysregulation is implicated in brain dysmaturation following preterm birth

https://doi.org/10.1016/j.bbi.2020.09.007Get rights and content
Under a Creative Commons license
open access

Highlights

  • Elevated IL-8 is a characteristic feature of intrauterine inflammation in the context of preterm birth.

  • IL-8 concentration is associated with neurite density in preterm infants at term-equivalent age.

  • IL-8 dysregulation links systemic inflammation and preterm brain dysmaturation.

Abstract

Background

Preterm birth is associated with dysconnectivity of structural brain networks, impaired cognition and psychiatric disease. Systemic inflammation contributes to cerebral dysconnectivity, but the immune mediators driving this association are poorly understood. We analysed information from placenta, umbilical cord and neonatal blood, and brain MRI to determine which immune mediators link perinatal systemic inflammation with dysconnectivity of structural brain networks.

Methods

Participants were 102 preterm infants (mean gestational age 29+1 weeks, range 23+3-32+0). Placental histopathology identified reaction patterns indicative of histologic chorioamnionitis (HCA), and a customized immunoassay of 24 inflammation-associated proteins selected to reflect the neonatal innate and adaptive immune response was performed from umbilical cord (n = 55) and postnatal day 5 blood samples (n = 71). Brain MRI scans were acquired at term-equivalent age (41+0 weeks [range 38+0-44+4 weeks]) and alterations in white matter connectivity were inferred from mean diffusivity and neurite density index across the white matter skeleton.

Results

HCA was associated with elevated concentrations of C5a, C9, CRP, IL-1β, IL-6, IL-8 and MCP-1 in cord blood, and IL-8 concentration predicted HCA with an area under the receiver operator curve of 0.917 (95% CI 0.841 – 0.993, p < 0.001). Fourteen analytes explained 66% of the variance in the postnatal profile (BDNF, C3, C5a, C9, CRP, IL-1β, IL-6, IL-8, IL-18, MCP-1, MIP-1β, MMP-9, RANTES and TNF-α). Of these, IL-8 was associated with altered neurite density index across the white matter skeleton after adjustment for gestational age at birth and at scan (β = 0.221, p = 0.037).

Conclusions

These findings suggest that IL-8 dysregulation has a role in linking perinatal systemic inflammation and atypical white matter development in preterm infants.

Keywords

Preterm
Neonate
Inflammation
Interleukin-8
Magnetic resonance imaging
Brain

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